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Flavie Perrier,1 Reza Ghiasvand,2,3 Simon Lergenmuller,1 Trude E Robsahm,3 Adele C Green,4,5 Kristin B Borch,6 Torkjel M Sandanger,6 Elisabete Weiderpass,7 Corina S Rueegg,2 Marit B Veierød1 1Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway; 2Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway; 3Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway; 4QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; 5Cancer Research UK Manchester and Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; 6Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway; 7International Agency for Research on Cancer, Lyon, FranceCorrespondence: Flavie Perrier, Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, PO Box 1122, Blindern, Oslo, N-0317, Norway, Email flavie.perrier@medisin.uio.noPurpose: Physical activity (PA) is a cornerstone in disease prevention and varies throughout life. A pooled analysis of cohort studies and a meta-analysis of cohort studies found positive associations between PA and melanoma risk. However, previous studies focused on PA at specific ages and often lacked information on ultraviolet radiation (UVR) exposure. Using the population-based Norwegian Women and Cancer (NOWAC) cohort, including information on PA and UVR exposure, we estimated life-course PA trajectories from adolescence to adulthood and their associations with melanoma.Methods: Total PA across different domains (recreation, occupation, transport, household) was reported for ages 14 and 30 years, and when responding to the questionnaire (31– 76 years) using a 10-point scale, validated to rank PA levels in Norwegian females. We estimated life-course PA trajectories using a latent class mixed model in 152,248 women divided into three subcohorts depending on age at questionnaire completion: 31– 39 (n = 27,098), 40– 49 (n = 52,515) and ≥ 50 years (n = 72,635). The unique 11-digit identity number of Norwegian citizens was used to link NOWAC to the Cancer Registry of Norway for information on cancer diagnoses, emigration and death. Associations between PA trajectories and melanoma risk were estimated in each subcohort using multivariable Cox regression.Results: Five classes of individual life-course PA trajectories were identified in subcohort 31– 39 years (low, moderate, high, decreasing, increasing PA) and four in subcohorts 40– 49 and ≥ 50 years (low, moderate, high, decreasing PA). No significant association was found between life-course PA trajectories and melanoma risk in any subcohort. Hazard ratios (95% confidence intervals) for the high versus moderate trajectory were 0.92 (0.66– 1.29), 1.15 (0.97– 1.37) and 0.90 (0.78– 1.05) for subcohorts 31– 39, 40– 49 and ≥ 50 years, respectively.Conclusion: Our results do not support a positive association between PA and melanoma risk found in previous studies, which is important for public health guidelines promoting regular PA.Keywords: physical activity, cutaneous melanoma, trajectory, cohort, women, Norway

Objectives Human papillomavirus (HPV) infections are common, especially during women’s reproductive years, with unclear obstetrical impact. This study aimed to identify HPV prevalence at mid-gestation and delivery, type-specific persistence from mid-gestation to delivery, and risk factors for HPV infection and persistence. Methods In 757 women from a Scandinavian prospective mother–child cohort, HPV was analyzed in first-void urine samples at mid-gestation and delivery. We used Seegene Anyplex II HPV28 PCR assay for genotyping and semi-quantifying 28 genital HPV genotypes, including 12 high-risk HPVs (HR-HPV). Socio-demographic and health data were collected through e-questionnaires. Results Any-HPV genotype (any of 28 assessed) was detected in 38% of the study cohort at mid-gestation and 28% at delivery, and HR-HPVs in 24% and 16%, respectively. The most prevalent genotype was HPV16: 6% at mid-gestation and 4% at delivery. Persistence of Any-HPV genotype was 52%, as was HR-HPV genotype-specific persistence. A short pre-conception relationship with the child’s father and alcohol intake during pregnancy increased HPV infection risk at both time points. Low viral load at mid-gestation was associated with clearance of HPV infections at delivery. Conclusion HPV prevalence was higher at mid-gestation compared with delivery, and low viral load was associated with clearance of HPV at delivery.

Background: Childhood cancer survivors are at risk for cardiovascular disease (CVD) because of intensive cancer therapies often accompanied by an unhealthy lifestyle. This study was aimed at 1) describing modifiable CVD risk factors in survivors and 2) investigating the association between different aspects of physical fitness and CVD risk factors.Methods: The authors analyzed cross-sectional data from ≥5-year survivors who were 16 years old or younger at their cancer diagnosis and 16 years old or older at the time of the study. Single CVD risk factors (waist circumference, blood pressure, fasting glucose, inverse high-density lipoprotein, and triglycerides), a composite CVD risk score (combined z scores of all CVD risk factors), and metabolic syndrome were evaluated. Physical fitness measures included cardiopulmonary exercise testing (CPET), a handgrip test, and a 1-minute sit-to-stand test (STS). Multivariable logistic regression was used for the association between fitness measures and CVD risk factors, with adjustments made for demographic factors and cancer therapy.Results: This study included 163 survivors with a median age at diagnosis of 7 years and a median age at the time of the study of 28 years. Among those survivors, 27% had a high waist circumference, 32% had high blood pressure, 19% had high triglycerides, 20% had an increased composite CVD risk score, and 10% had metabolic syndrome. A better performance during CPET, handgrip testing, and STS was associated with a lower probability of having a high waist circumference, high triglycerides, and metabolic syndrome.Conclusions: Better aerobic fitness (CPET) and, to a lesser extent, handgrip and STS were associated with fewer CVD risk factors. Further investigations are warranted to investigate which fitness measures should preferably be used to screen survivors to promote physical activity in those with impaired test performance. Lay Summary: This study investigated the relationship between physical fitness of adult childhood cancer survivors and their risk factors for cardiovascular disease. Cardiovascular risk factors such as high blood pressure, a high waist circumference, and high blood lipids were frequently found in childhood cancer survivors. Survivors with better physical fitness (measured by a cycling test or simple strength and endurance tests) had a lower chance of having cardiovascular risk factors. This suggests that childhood cancer survivors could benefit from physical activity and general fitness by increasing their physical fitness and possibly decreasing their risk of cardiovascular disease.

Childhood cancer survivors (CCS) are at risk of reduced bone health and premature osteoporosis. As physical activity with high impact loading (IL-PA) is known to promote bone health, we compared bone densitometry and microstructure between groups of CCS who performed different amounts of physical activities in their daily life. We used baseline data of a single-center PA trial including 161 CCS from the Swiss Childhood Cancer Registry, aged16 at diagnosis, ≥16 at study and ≥5 years since diagnosis. Lower body bone health was assessed with peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA). Daily IL-PA (duration in activities2 g acceleration and numbers of vertical impacts/hr2 g) was captured using hip-worn accelerometers (1-3 weeks). For both IL-PA approaches, we formed low, middle and high activity groups based on tertiles. Bone health of the high and middle active groups was compared to the low active group. 63% of CCS had indication of at least one bone mineral density z-score ≤ -1 measured by pQCT or DXA. The high IL-PA group performing 2.8 min/day or 19.1 impact peaks/hr 2 g (median) showed about 3-13% better microstructural and densitometric bone health as compared to the low IL-PA group with 0.38 min/day or 0.85 peaks/hr 2 g. Just a few minutes and repetitions of high IL-PA as easily modifiable lifestyle factor may be sufficient to improve bone health in adult CCS. Future longitudinal research is needed to better understand pattern and dosage of minimal impact loading needed to strengthen bone in growing and adult CCS.

Knowledge about factors associated with melanoma thickness, the most important prognostic factor for localized primary melanoma survival,1 may help reduce the risk of melanoma deaths. Previously reported associations of melanoma thickness with pigmentary characteristics, number of naevi, diet quality and body mass index (BMI)2–4 may be explained by behavioural and biological mechanisms. Physical activity (PA) has been associated with improved outcomes for several cancers,5 but its relation with melanoma thickness and prognosis is unknown.

Background Research indicates reduced physical performance from diagnosis into survivorship of pediatric cancer patients. However, there is no systematic information or guideline available on the methods to assess physical performance and function in this population. The purpose was to systematically compile and describe assessments of physical performance and function in patients and survivors of pediatric cancer, including cardiorespiratory fitness, muscle strength, speed, balance, flexibility, functional mobility, gait and motor performance test batteries. Methods We searched the databases PubMed, SPORTDiscus, and Cochrane Database and performed abstract and full-text selection of 2619 articles according to the Cochrane Handbook of Systematic Reviews. Information on patients characteristics, assessments, information on validity and reliability, and relevant references was extracted. Results In summary, 63 different assessments were found in 149 studies including 11639 participants. Most studies evaluated cardiorespiratory fitness and muscle strength with the majority conducted off treatment. Some outcomes (e.g. speed) and diagnoses (e.g. neuroblastoma) were severely underrepresented. With the exception of gait, leukemia patients represented the largest group of individuals tested. Conclusions Insufficient data and patient heterogeneity complicate uniform recommendations for assessments. Our results support researchers and practitioners in selecting appropriate assessment to meet their specific research questions or individual daily practice needs. Impact This systematic review includes 149 studies and provides a comprehensive summary of 63 assessments to evaluate cardiorespiratory fitness, muscle strength, speed, balance, flexibility, functional mobility, gait or motor performance test batteries in patients and survivors of pediatric cancer. We present the most studied fields within the pediatric cancer population, which are cardiorespiratory fitness and muscle strength, off treatment phase, and leukemia patients. We propose research priorities by identification of subgroups in terms of cancer type, phase of treatment, and outcome of interest that are underrepresented in studies currently available.

Background Petrochemical workers are exposed to a variety of airborne toxic compounds which have been associated with increased risk for respiratory outcomes. However, long-term exposure to SO2, NO2, O3, H2S and NH3 in relation to spirometric parameters and self-reported respiratory problems is largely unknown. Methods Airborne concentration levels of SO2, NO2, O3, H2S and NH3 were collected from two fixed stations over a 3-year period in a petrochemical complex. We assessed spirometric parameters and respiratory symptoms in the petrochemical workers (n = 200) and in an unexposed group (n = 200). We calculated β-coefficients (β) and odds ratios (ORs) with 95% confidence intervals (CIs) before and after adjustment for covariates. Results The mean airborne pollution levels were 159 µg/m3 for SO2, 43 µg/m3 for NO2, 66 µg/m3 for O3, 6 µg/m3 for H2S, and 24 µg/m3 for NH3. We found a significant reduction in spirometric parameters among petrochemical workers compared to the unexposed: FEV1 (forced expiratory volume in 1s) (adjusted β -12; 95%CI -16, -7.64), FEV1/ FVC (forced vital capacity) (β -7.26; 95%CI -9.23, -5.28), and PEF (peak expiratory flow) (β -6.61; 95%CI -12, -0.76). Additionally, we observed higher adjusted risks for any respiratory symptom (OR 4.69; 95%CI 1.76, 12), mucus (OR 4.36; 95%CI 1.70, 11) and shortness of breath (OR 15; 4.95, 46) among petrochemical workers compared to the unexposed group. Conclusions Most measured airborne pollution levels were within the ambient recommendation levels. Still, long-term exposure to low level airborne pollutants, reduced FEV1, FEV1/FVC and PEF, and increased respiratory symptoms in Iranian petrochemical workers compared to unexposed controls.

Purpose Declining response rates threaten the generalizability of health surveys. We investigate (1) the effect of item order on response rate; (2) characteristics of early , late and non-responders; and (3) potential non-response bias in a population-based health survey of childhood, adolescent and young adult cancer survivors (CAYACS). Methods We mailed a questionnaire survey to 5361 eligible CAYACS identified by the Cancer Registry of Norway (CRN), representing a range of cancer diagnoses. The 302-item questionnaire included a range of survivorship-related questions and validated patient-reported outcome measures. To investigate item-order effects on response rates, we constructed two versions of the questionnaire presenting cancer-related or socio-demographic items first. The CRN provided demographic and clinical information for the total population. Risk of non-response bias was estimated by (1) comparing outcomes between early and late responders (answered after a reminder), and (2) by applying inverse probability of participation weights to construct a total population (with 100% response) and then compare 21 a priori selected outcomes between early responders, all responders (early + late) and the total population (all eligible). Results Survey item order did not affect response rates (cancer first 49.8% vs socio-demographic first 50.2%). Shorter time since diagnosis, male gender and a malignant melanoma diagnosis remained significant predictors of non-response in a multivariable multinomial regression model. There were no significant differences on 16/21 survey outcomes between early and late responders, and 18/21 survey outcomes between early responders, all responders and the total population. Conclusion Despite a modest response rate, we found little evidence for a response bias in our study. Implications for Cancer Survivors Surveys of survivor-reported outcomes with low response rates may still be valuable and generalizable to the total survivor population.

This is the peer reviewed version of the following article: Jalilian, H., Ziaei, M., Weiderpass, E., Rueegg, C. S., Khosravi, Y. & Kjærheim, K. (2019). Cancer incidence and mortality among firefighters. International Journal of Cancer, 145(10), 2639-2646., which has been published in final form at https://doi.org/10.1002/ijc.32199

Evidence on sunscreen use and cutaneous squamous cell carcinoma (cSCC) risk is limited. Most studies have not taken sun protection factor (SPF) into consideration and used nonusers of sunscreen as the reference group. Nonusers are likely a priori at lower cSCC risk than users. No study has investigated the effect of high- versus low-SPF sunscreens on cSCC, appropriately adjusting for time-varying confounding. Using data from the Norwegian Women and Cancer Study (1991–2016), we investigated whether use of SPF ≥15 versus SPF

Physical activity (PA) is an important factor in cancer prevention, but positive association between PA and risk of cutaneous melanoma found in recent studies may complicate this strategy. Ultraviolet radiation (UVR) exposure during outdoor PA is a plausible explanation for a positive association. We investigated the associations between PA, UVR and melanoma risk in the Norwegian Women and Cancer cohort. Overall PA was reported by 151,710 women, aged 30–75 at inclusion, using a validated 10-point-scale at enrolment and during follow-up, together with recent numbers of sunburns, indoor tanning sessions and weeks on sunbathing vacations. Seasonal outdoor walking and seasonal PAs were recorded in subsamples (n = 102,671 and n = 29,077, respectively). Logistic and Cox regression were used. Mean follow-up was 18.5 years, and 1565 invasive incident melanoma cases were diagnosed. Overall PA was inversely associated with sunburns, while positively associated with sunbathing vacations and indoor tanning. Overall PA was not associated with melanoma risk in all body sites combined (ptrend = 0.61), but reduced risk was found in upper limb melanomas (hazard ratio (HR) = 0.70, 95% confidence interval (CI) 0.51–0.96; high versus low PA). Non-significant reduced risks were found for seasonal outdoor walking >2 h/day versus 30–60 min/day (summer HR = 0.81, 95% CI 0.66–1.00; autumn HR = 0.74, 95%CI 0.55–1.01). Seasonal PAs were not associated with melanoma risk. In conclusion, we found positive associations between overall PA and sunbathing vacations and indoor tanning, and, unlike literature, inverse association between overall PA and sunburns. Our results do not support a positive association between PA and melanoma risk in Norwegian women.

Host-directed-therapy strategies are warranted to fight tuberculosis. Here we assess the safety and immunogenicity of adjunctive vaccination with the H56:IC31 candidate and cyclooxygenase-2-inhibitor treatment (etoricoxib) in pulmonary and extra-pulmonary tuberculosis patients in a randomized open-label phase I/II clinical trial (TBCOX2, NCT02503839). A total of 222 patients were screened, 51 enrolled and randomized; 13 in the etoricoxib-group, 14 in the H56:IC31-group, 12 in the etoricoxib+H56:IC31-group and 12 controls. Three Serious Adverse Events were reported in the etoricoxib-groups; two urticarial rash and one possible disease progression, no Serious Adverse Events were vaccine related. H56:IC31 induces robust expansion of antigen-specific T-cells analyzed by fluorospot and flow cytometry, and higher proportion of seroconversions. Etoricoxib reduced H56:IC31-induced T-cell responses. Here, we show the first clinical data that H56:IC31 vaccination is safe and immunogenic in tuberculosis patients, supporting further studies of H56:IC31 as a host-directed-therapy strategy. Although etoricoxib appears safe, our data do not support therapy with adjunctive cyclooxygenase-2-inhibitors., Modulating the host immune response during tuberculosis is an emerging and critical advance in the therapeutic approach. Here the authors present data from a first-in-human phase I/II randomised trial on the safety and immunogenicity of adjuvant therapy of the H56:IC31 vaccine and cyclooxygenase-2 inhibitors in patients with tuberculosis.

The recent launch of the first point-of-care Xpert® hepatitis B virus (HBV) viral load kit from Cepheid could help to scale up treatment for chronic hepatitis B (CHB) in resource-limited settings. This study aimed to assess the performance of the Xpert kit under field conditions in Ethiopia. One-hundred-and-thirty CHB patients with viral loads ranging from 7 log10 IU/mL were randomly sampled. The viral load was assessed with both the Xpert and the gold standard Abbott RealTime HBV Viral Load assay in each patient. There was a high correlation between the viral loads assessed by Xpert and Abbott (r = 0.948, p 1 log10 IU/mL. Using the treatment threshold of 2000 IU/mL in both tests, Xpert had a sensitivity of 94 %, specificity of 71 %, positive predictive value of 70 %, and negative predictive value of 95 %. In conclusion, the Xpert kit demonstrated good validity for the measurement of HBV viral load in a real-life setting.

Here, we randomized 53 patients hospitalized with coronavirus disease 2019 (COVID-19) to hydroxychloroquine therapy (at a dose of 400 mg twice daily for seven days) in addition to standard care or standard care alone (ClinicalTrials.gov Identifier, NCT04316377). All severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients 18 years of age or older were eligible for study inclusion if they had moderately severe COVID-19 at admission. Treatment with hydroxychloroquine did not result in a significantly greater rate of decline in SARS-CoV-2 oropharyngeal viral load compared to standard care alone during the first five days. Our results suggest no important antiviral effect of hydroxychloroquine in humans infected with SARS-CoV-2., The use of hydroxychloroquine therapy for the treatment of Covid-19 is controversial. In this study, Lyngbakken and colleagues present a randomized controlled trial and show that the drug has no antiviral effects in humans infected with SARS-CoV-2.

Purpose The majority of childhood, adolescent, and young adult cancer survivors (CAYACS) are at risk of late effects but may not receive long-term follow-up care for these. Here, we investigated (1) self-reported late effects, (2) long-term follow-up care, and (3) factors associated with receiving follow-up care in a population-based sample of Norwegian long-term CAYACS. Methods Survivors were identified by the Cancer Registry of Norway. All > 5-year survivors diagnosed between 1985 and 2009 with childhood cancer (CCS, 0–18 years old, excluding CNS), breast cancer (BC, stages I–III), colorectal cancer (CRC), leukemias (LEUK), non-Hodgkin lymphoma (NHL), or malignant melanoma (MM) at age 19–39 years were mailed a questionnaire (NOR-CAYACS study). Descriptive statistics and logistic regression models were used to analyze occurrence of late effects, long-term follow-up care for these, and associated factors. Results Of 2104 responding survivors, 1889 were eligible for analyses. Of these, 68% were females, with a mean age of 43 years at survey, on average 17 years since diagnosis, and diagnosed with CCS (31%), BC (26%), CRC (8%), NHL (12%), LEUK (7%), and MM (16%). Overall, 61.5% reported the experience of at least one late effect, the most common being concentration/memory problems (28.1%) and fatigue (25.2%). Sixty-nine percent reported not having received long-term follow-up care focusing on late effects. Lower age at survey (p = 0.001), higher education (p = 0.012), and increasing number of late effects (p = < 0.001) were associated with increased likelihood of follow-up care in the multivariate model. Conclusions The majority of survivors reported at least one late effect, but not receiving specific follow-up care for these. This indicates a need for structured models of long-term follow-up to ensure adequate access to care.

Final version with altered title. Importance - No study, to our knowledge, has prospectively investigated a dose-response association between lifetime indoor tanning and risk of cutaneous squamous cell carcinoma (SCC). Objective - To investigate the dose-response association between lifetime indoor tanning and SCC risk, the association between duration of use and age at initiation with SCC risk, and the association between age at initiation and age at diagnosis. Design, Setting, and Participants - This cohort study included data from women born from 1927 to 1963 from the Norwegian Women and Cancer study, established in 1991 with follow-up through December 31, 2015. Baseline questionnaires were issued to participants from 1991 to 2007, with follow-up questionnaires given every 5 to 7 years. Data analysis was performed from January 2, 2018, to March 2, 2019. Exposures - Participants reported pigmentation factors. Sunburns, sunbathing vacations, and indoor tanning were reported for childhood, adolescence, and adulthood. Main Outcomes and Measures - Information on all cancer diagnoses and dates of emigration or death were obtained through linkage to the Cancer Registry of Norway, using the unique personal identification number of Norwegian citizens. Results - A total of 159 419 women (mean [SD] age at inclusion, 49.9 [8.3] years) were included in the study. During follow-up (mean [SD], 16.5 [6.4] years), 597 women were diagnosed with SCC. Risk of SCC increased with increasing cumulative number of indoor tanning sessions. The adjusted hazard ratio (HR) for highest use vs never use was 1.83 (95% CI, 1.38-2.42; P Conclusion and Relevance - The findings provide supporting evidence that there is a dose-response association between indoor tanning and SCC risk among women. The association between cumulative exposure to indoor tanning and SCC risk was the same regardless of duration of use and age at initiation. These results support development of policies that regulate indoor tanning.

OBJECTIVES In the national newborn screening programme for CF in Switzerland, we compared the performance of two sweat test methods, by investigating the feasibility and diagnostic performance of the Macroduct collection method (with chloride mesurement) and Nanoduct test (measuring conductivity) for diagnosing CF. STUDY-DESIGN We included all newborns with a positive screening result between 2011 and 2015 who were referred to a CF-centre for sweat testing. In the CF-centre, a Macroduct and Nanoduct sweat test were performed simultaneously. If sweat test results were positive or borderline, a DNA analysis was performed. Final diagnosis was based on genetic mutations. RESULTS Over 5 years, 445 children were screened positive and in 413 (114 with CF) at least one sweat test was performed (median age at first test, 22 days); both tests were performed in 371 children. A sweat test result was more often available with the Nanoduct compared to the Macroduct (79 vs 60%, P

Whether sunscreen use affects melanoma risk has been widely studied with contradictory results. To answer this question we performed a systematic review of all published studies, accounting for sources of heterogeneity and bias. We searched for original articles investigating the sunscreen‐melanoma association in humans to February 28, 2018. We then used random‐effects meta‐analysis to combine estimates of the association, stratified by study design. Stratified meta‐analysis and meta‐regression were used to identify sources of heterogeneity. We included 21,069 melanoma cases from 28 studies published 1979–2018: 23 case–control (11 hospital‐based, 12 population‐based), 1 ecological, 3 cohort and 1 randomised controlled trial (RCT). There was marked heterogeneity across study designs and among case–control studies but adjustment for confounding by sun exposure, sunburns and phenotype systematically moved estimates toward decreased melanoma risk among sunscreen users. Ever‐ vs. never‐use of sunscreen was inversely associated with melanoma in hospital‐based case–control studies (adjusted odds ratio (OR) = 0.57, 95%confidence interval (CI) 0.37–0.87, p heterogeneity < 0.001), the ecological study (rate ratio = 0.48, 95%CI 0.35–0.66), and the RCT (hazard ratio (HR) = 0.49, 95%CI 0.24–1.01). It was not associated in population‐based case–control studies (OR = 1.17, 95%CI 0.90–1.51, p heterogeneity < 0.001) and was positively associated in the cohort studies (HR = 1.27, 95%CI 1.07–1.51, p heterogeneity = 0.236). The association differed by latitude (p interaction = 0.042), region (p interaction = 0.008), adjustment for naevi/freckling (p interaction = 0.035), and proportion of never‐sunscreen‐users (p interaction = 0·012). Evidence from observational studies on sunscreen use and melanoma risk was weak and heterogeneous, consistent with the challenges of controlling for innate confounding by indication. The only RCT showed a protective effect of sunscreen., What's new? Effectiveness of sunscreen in reducing UV‐induced skin damage has been proven in experimental studies, but effectiveness in reducing melanoma in humans remains inconclusive. This is the first meta‐analysis to analyze data from four study designs, stratify hospital‐ and population‐based case–control studies, and include as many as five prospective studies. Evidence from observational studies on the sunscreen‐melanoma association was heterogeneous, consistent with the challenges of controlling for innate confounding by indication. The only randomized controlled trial showed a protective effect. Public health recommendations should place greater emphasis on the proper use of sunscreen in conjunction with other means of sun protection.

PURPOSE. To investigate fundus autofluorescence (FAF) and other fundus manifestations in congenital aniridia. METHODS. Fourteen patients with congenital aniridia and 14 age- and sex-matched healthy controls were examined. FAF images were obtained with an ultra-widefield scanning laser ophthalmoscope. FAF intensity was quantified in the macular fovea and in a macular ring surrounding fovea and related to an internal reference within each image. All aniridia patients underwent an ophthalmologic examination, including optical coherence tomography and slitlamp biomicroscopy. RESULTS. Mean age was 28.4 +/- 15.0 years in both the aniridia and control groups. Fovea could be defined by subjective assessment of FAF images in three aniridia patients (21.4%) and in all controls (P = 0.001). Mean ratio between FAF intensity in the macular ring and fovea was 1.01 +/- 0.15 in aniridia versus 1.18 +/- 0.09 in controls (P = 0.034). In aniridia, presence of foveal hypoplasia evaluated by biomicroscopy correlated with lack of foveal appearance by subjective analyses of FAF images (P = 0.031) and observation of nystagmus (P = 0.009). CONCLUSIONS. Aniridia patients present a lower ratio between FAF intensity in the peripheral and central macula than do healthy individuals. Both subjective and objective analyses of FAF images are useful tools in evaluation of foveal hypoplasia in aniridia. Funding Agencies|Aniridia Norway (Oslo, Norway); Jon Larsen foundation (Tonsberg, Norway); Inger Holms memorial foundation (Oslo, Norway); Norwegian Association of the Blind and Partially Sighted (Oslo, Norway); Norwegian Ophthalmological Society (Oslo, Norway); Department of Ophthalmology at Oslo University Hospital (Oslo, Norway); National Centre for Optics, Vision and Eye Care at the University of South-Eastern Norway; European Union Seventh Framework Program (FP7-PEOPLE-2013-COFUND) [609020]

Rationale While recent studies show that maternal use of snus during pregnancy is increasing, the potential effects on infant birth size is less investigated, with conflicting results. Objectives We aimed to determine if maternal use of snus during pregnancy influences the infant anthropometric and proportional size measures at birth. Methods In 2313 mother–child pairs from the population-based, mother–child birth cohort PreventADALL (Preventing Atopic Dermatitis and ALLergies) in Norway and Sweden, we assessed nicotine exposure by electronic questionnaire(s) at 18 and 34 weeks of pregnancy, and anthropometric measurements at birth. Associations between snus exposure and birth size outcomes were analysed by general linear regression. Results Birthweight was not significantly different in infants exposed to snus in general, and up to 18 weeks of pregnancy in particular, when adjusting for relevant confounders including maternal age, gestational age at birth, pre-pregnancy body mass index, parity, fetal sex and maternal gestational weight gain up to 18 weeks. We found no significant effect of snus use on the other anthropometric or proportional size measures in multivariable linear regression models. Most women stopped snus use in early pregnancy. Conclusion Exposure to snus use in early pregnancy, with most women stopping when knowing about their pregnancy, was not associated with birth size. We were unable to conclude on effects of continued snus use during pregnancy because of lack of exposure in our cohort., Snus use in pregnancy, reported by 7.1% of 2313 women, was not associated with infant birth size. As most women stopped snus use by 6 weeks gestational age, it was not possible to assess potential birth size effects of persistent use during pregnancy. http://bit.ly/2IG8Vnk

Purpose: As survival rates of adolescent and young adult (AYA) cancer patients increase, a growing number of AYA cancer survivors need follow-up care. However, there is little research on their preferences for follow-up care. We aimed to 1) describe AYA cancer survivors' preferences for the organization and content of follow-up care; 2) describe their preferences for different models of follow-up; and 3) investigate clinical and socio-demographic characteristics associated with preferences for the different models. Methods: AYA cancer survivors (diagnosed with cancer at age 16-25 years; ≥5 years after diagnosis) were identified through the Cancer Registry Zurich and Zug. Survivors completed a questionnaire on follow-up attendance, preferences for organizational aspects of follow-up care (what is important during follow-up, what should be included during appointments, what specialists should be involved, location), models of follow-up (telephone/questionnaire, general practitioner (GP), pediatric oncologist, medical oncologist, multi-disciplinary team) and sociodemographic characteristics. Information on tumor and treatment was available through the Cancer Registry Zurich and Zug. Results: Of 389 contacted survivors, 160 (41.1%) participated and 92 (57.5%) reported still attending follow-up. Medical aspects of follow-up care were more important than general aspects (p

In this study, we investigated whether childhood cancer survival in Switzerland is influenced by socioeconomic status (SES), and if disparities vary by type of cancer and definition of SES (parental education, living condition, area-based SES). Using Cox proportional hazards models, we analyzed 5-year cumulative mortality in all patients registered in the Swiss Childhood Cancer Registry diagnosed 1991-2006 below 16 years. Information on SES was extracted from the Swiss census by probabilistic record linkage. The study included 1602 children (33% with leukemia, 20% with lymphoma, 22% with central nervous system (CNS) tumors); with an overall 5-year survival of 77% (95%CI 75-79%). Higher SES, particularly parents' education, was associated with a lower 5-year cumulative mortality. Results varied by type of cancer with no association for leukemia and particularly strong effects for CNS tumor patients, where mortality hazard ratios for the different SES indicators, comparing the highest with the lowest group, ranged from 0.48 (95%CI: 0.28-0.81) to 0.71 (95%CI: 0.44-1.15). We conclude that even in Switzerland with a high quality health care system and mandatory health insurance, socioeconomic differences in childhood cancer survival persist. Factors causing these survival differences have to be further explored, to facilitate universal access to optimal treatment and finally eliminate social inequalities in childhood cancer survival.

Perinatal asphyxia is a severe medical condition resulting from oxygen deficiency (hypoxia) at the time of birth, causing worldwide approximately 680,000 newborn deaths every year. Better prediction of severity of damages including early biomarkers is highly demanded. Elevated levels of circulating cell-free DNA (cfDNA) in blood have been reported for a range of different diseases and conditions, including cancer and prematurity. The objective of this study was to validate methods for assessing cfDNA in blood and cerebrospinal fluid (CSF) and to explore temporal variations in a piglet model of neonatal hypoxia-reoxygenation. Different cfDNA extraction methods in combination with cfDNA detection systems were tested, including a fluorescent assay using SYBR Gold and a qRT-PCR-based technique. Newborn piglets (n = 55) were exposed to hypoxia-reoxygenation, hypoxia-reoxygenation and hypothermia, or were part of the sham-operated control group. Blood was sampled at baseline and at post-intervention, further at 30, 270, and 570 minutes after the end of hypoxia. Applying the fluorescent method, cfDNA concentration in piglets exposed to hypoxia (n = 32) increased from 36.8±27.6 ng/ml prior to hypoxia to a peak level of 61.5±54.9 ng/ml after the intervention and deceased to 32.3±19.1 ng/ml at 570 minutes of reoxygenation, whereas the group of sham-operated control animals (n = 11) revealed a balanced cfDNA profile. Animals exposed to hypoxia and additionally treated with hypothermia (n = 12) expressed a cfDNA concentration of 54.4±16.9 ng/ml at baseline, 39.2±26.9 ng/ml at the end of hypoxia, and of 41.1±34.2 ng/ml at 570 minutes post-intervention. Concentrations of cfDNA in the CSF of piglets exposed to hypoxia revealed at post-intervention higher levels in comparison to the controls. However, these observations were only tendencies and not significant. In a first methodological proof-of-principle study exploring cfDNA using a piglet model of hypoxia-reoxygenation variations in the temporal patterns suggest that cfDNA might be an early indicator for damages caused by perinatal asphyxia.

Knowledge on former diagnosis, treatment and survivorship is important for adolescent and young adult cancer survivors (AYACS) to make informed healthcare decisions. We aimed to (a) describe the information AYACS reported to have received, (b) identify current information needs and survivors' preferred format of communication, and (c) examine associations between information needs and cancer-related/socio-demographic characteristics, psychological distress and health-related quality of life (HRQoL). We identified AYACS (16-25 years at diagnosis; ≥5 years since diagnosis) through the Cancer Registry Zurich and Zug. Survivors received a questionnaire on information received and current information needs, socio-demographic information, psychological distress (Brief Symptom Inventory-18) and HRQoL (SF-12). Clinical characteristics were available from the cancer registry. We used descriptive statistics and univariable regression models. Of 160 responders, most reported to have received information on disease (96.3%), treatment (96.3%) and follow-up (89.4%), fewer on late effects (63.1%). Survivors reported information needs on late effects (78.7%), follow-up (71.3%), disease (58.1%) and treatment (55.6%). Information needs were associated with experiencing psychological distress and lower mental HRQoL. Most Swiss AYACS have information needs, especially on follow-up and late effects. Therefore, AYACS should be personally, continuously and proactively informed about their disease, treatment, follow-up care and late effects.

Source at https://doi.org/10.1001/jamadermatol.2018.3964. Importance: Two pathways have been hypothesized for the development of cutaneous melanoma: one typically affects the head and neck, a site with chronic sun damage, and the other affects the trunk, which is less exposed to the sun. However, the possible cause of limb melanomas is less studied under this hypothesis. Objective: To investigate the association between phenotypic characteristics, pattern of UV radiation exposure, and risk of melanoma on different body sites. Design, Setting, and Participants: This study used data on 161 540 women with information on phenotypic characteristics and UV radiation exposure who were part of the Norwegian Women and Cancer study, a population-based prospective study established in 1991 with exposure information collected by questionnaires at baseline and every 4 to 6 years during follow-up through 2015. Data analysis was performed from October 2017 through May 2018. Exposures: Participants reported hair color, eye color, untanned skin color, number of small symmetric and large asymmetric nevi, and freckling, as well as histories of sunburns, sunbathing vacations, and indoor tanning in childhood, adolescence, and adulthood. Main Outcomes and Measures: The Norwegian Women and Cancer study was linked to the Cancer Registry of Norway for data on cancer diagnosis and date of death or emigration. Primary melanoma site was categorized as head and neck, trunk, upper limbs, and lower limbs. Results: During follow-up of the 161 540 women in the study (mean age at study entry, 50 years [range, 34-70 years]; mean age at diagnosis, 60 years [range, 34-87 years]), 1374 incident cases of melanoma were diagnosed. Having large asymmetric nevi was a significant risk factor for all sites and was strongest for the lower limbs (relative risk [RR], 3.38; 95% CI, 2.62-4.38) and weakest for the upper limbs (RR, 1.96; 95% CI, 1.22-3.17; P = .02 for heterogeneity). Mean lifetime number of sunbathing vacations was significantly associated with risk of trunk melanomas (RR, 1.14; 95% CI, 1.07-1.22) and lower limb melanomas (RR, 1.12; 95% CI, 1.05-1.19) but not upper limb melanomas (RR, 0.98; 95% CI, 0.88-1.09) and head and neck melanomas (RR, 0.87; 95% CI, 0.73-1.04; P = .006 for heterogeneity). Indoor tanning was associated only with trunk melanomas (RR for the highest tertile, 1.49; 95% CI, 1.16-1.92) and lower limb melanomas (RR for the highest tertile, 1.33; 95% CI, 1.00-1.76; P = .002 for heterogeneity). Skin color, hair color, small symmetric nevi, and history of sunburns were associated with risk of melanoma on all sites. Conclusions and Relevance: These results appear to support the hypothesis of divergent pathways to melanoma and that recreational sun exposure and indoor tanning are associated with melanoma on the lower limbs, the most common site of melanoma in women. These findings appear to have important preventive implications.

Objective Investigate whether gastroenterologists rate the quality of referral letters higher if electronic dynamic checklist items are added to a standard free-text referral letter. Assess how this affects the gastroenterologists’ assessment of the patient’s need for healthcare and the agreement between their assessments. Design Randomized vignette study. Setting Norwegian primary gastroenterology services. Participants Thirty-two Norwegian gastroenterologists. Intervention Between June 2015 and January 2016, participants were recruited through an open invitation to all members of the Norwegian Society of Gastroenterology. They were asked to rate 16 referral letters (vignettes) in a web interface: eight letters in free text following a general template and eight letters based on a general referral template combined with diagnosis-specific checklist items. The study was completed in two subsequent rounds ≥3 months apart. Main Outcome Measures Quality of referral letters assessed on a rating scale from 0 to 10. Agreement in the referral assessment and accuracy of the selection of correct preliminary diagnosis and appropriate work-up. Results The mean quality assesses on the rating scale was 7.0 (95% confidence interval [CI] 6.8–7.2) for all letters combined (n = 511), 6.5(CI 6.2–6.8) for the free-text referrals (n = 256) and 7.5(CI 7.3–7.7) for the checklist referrals (n = 255) (P < 0.001, paired t-test). No difference was observed in the triage of the patients, but fewer gastroenterologists felt the need to collect additional information about the patients in the checklist group. Conclusion Checklist items may ease the assessment of the referrals for gastroenterologists. We were not able to show that checklists significantly influence the management of patients.

BACKGROUND Little is known about follow-up care attendance of adolescent survivors of childhood cancer, and which factors foster or hinder attendance. Attending follow-up care is especially important for adolescent survivors to allow for a successful transition into adult care. We aimed to (i) describe the proportion of adolescent survivors attending follow-up care; (ii) describe adolescents' health beliefs; and (iii) identify the association of health beliefs, demographic, and medical factors with follow-up care attendance. PROCEDURE Of 696 contacted adolescent survivors diagnosed with cancer at ≤16 years of age, ≥5 years after diagnosis, and aged 16-21 years at study, 465 (66.8%) completed the Swiss Childhood Cancer Survivor Study questionnaire. We assessed follow-up care attendance and health beliefs, and extracted demographic and medical information from the Swiss Childhood Cancer Registry. Cross-sectional data were analyzed using descriptive statistics and logistic regression models. RESULTS Overall, 56% of survivors reported attending follow-up care. Most survivors (80%) rated their susceptibility for late effects as low and believed that follow-up care may detect and prevent late effects (92%). Few (13%) believed that follow-up care is not necessary. Two health beliefs were associated with follow-up care attendance (perceived benefits: odds ratio [OR]: 1.56; 95% confidence interval [CI]: 1.07-2.27; perceived barriers: OR: 0.70; 95%CI: 0.50-1.00). CONCLUSIONS We show that health beliefs are associated with actual follow-up care attendance of adolescent survivors of childhood cancer. A successful model of health promotion in adolescent survivors should, therefore, highlight the benefits and address the barriers to keep adolescent survivors in follow-up care. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc.

BACKGROUND Parents' knowledge about cancer, treatment, potential late effects and necessary follow-up is important to reassure themselves and motivate their child to participate in regular follow-up. We aimed to describe (i) parents' perception of information received during and after treatment; (ii) parents' current needs for information today, and to investigate; and (iii) associations between information needs and socio-demographic and clinical characteristics. METHODS As part of the Swiss Childhood Cancer Survivor Study, a follow-up questionnaire was sent to parents of survivors, diagnosed < 16 years and after 1990, and aged 11-17 years at study. We assessed parents' perception of information received and information needs, concerns about consequences of the cancer and socio-demographic information. Information on clinical data was available from the Swiss Childhood Cancer Registry. RESULTS Of 309 eligible parents, 189 responded (67%; mean time since diagnosis: 11.3 years, SD = 2.5). Parents perceived to have received verbal information (on illness: verbal 91%, written 40%; treatment: verbal 88%, written 46%; follow-up: verbal 85% written 27%; late effects: verbal 75%, written 19%). Many parents reported current information needs, especially on late effects (71%). The preferred source was written general (28%) or verbal information (25%), less favored was online information (12%). Information needs were associated with migration background (P = 0.039), greater concerns about consequences of cancer (P = 0.024) and no information received (P = 0.035). CONCLUSION Parents reported that they received mainly verbal information. However, they still needed further information especially about possible late effects. Individual long-term follow-up plans, including a treatment summary, should be provided to each survivor, preferably in written format.

BACKGROUND Cognitive problems can have a negative effect on a person's education, but little is known about cognitive problems in young childhood cancer survivors (survivors). This study compared cognitive problems between survivors and their siblings, determined if cognitive problems decreased during recent treatment periods and identified characteristics associated with the presence of a cognitive problem in survivors. METHODS As part of the Swiss Childhood Cancer Survivor Study, a questionnaire was sent to all survivors, aged 8-20 years, registered in the Swiss Childhood Cancer Registry, diagnosed at age

BACKGROUND Regular follow-up care is essential for childhood cancer survivors, but we know little about physicians' experience with it. We aimed to describe: (1) involvement of Swiss physicians in follow-up care; (2) content of follow-up care provided; (3) problems encountered; and (4) additional resources needed. MATERIALS AND METHODS Within this cross-sectional survey we sent adapted questionnaires via professional associations to a sample of medical oncologists (MOs), paediatric oncologists (POs), general practitioners (GPs) and paediatricians (P) in Switzerland. Only oncologists involved in follow-up care were asked to report problems. GPs and Ps not involved in follow-up could indicate why. All physicians were asked about the content of follow-up care provided and additional resources needed. RESULTS A total of 183 physicians responded (27 MO, 13 PO, 122 GP, 21 P). Involved in follow-up were 81% of MOs, 85% of POs, 39% of GPs and 81% of Ps. Follow-up content differed between oncologists (MO and PO) and generalists (GP and P), with generalists examining or informing less in regard to the former cancer. POs reported more problems than MOs: many POs reported problems with transition of survivors to adult care (91%), and because of financial resources (73%) and time restraints (73%). MOs reported most problems during transition (23%). Not being aware of a survivor was the most common reason for GPs and Ps not participating in follow-up (74%). All groups reported a need for standardised protocols (85-91%) and specialised training (55-73%). GPs (94%) and Ps (100%) additionally desired more support from oncologists. CONCLUSIONS To improve quality and efficiency of follow-up care a national follow-up care model including standardised protocols and guidelines needs to be developed.

Purpose This is the first study to quantify potential nonresponse bias in a childhood cancer survivor questionnaire survey. We describe early and late responders and nonresponders, and estimate nonresponse bias in a nationwide questionnaire survey of survivors. Methods In the Swiss Childhood Cancer Survivor Study, we compared characteristics of early responders (who answered an initial questionnaire), late responders (who answered after ≥1 reminder) and nonresponders. Sociodemographic and cancer-related information was available for the whole population from the Swiss Childhood Cancer Registry. We compared observed prevalence of typical outcomes in responders to the expected prevalence in a complete (100% response) representative population we constructed in order to estimate the effect of nonresponse bias. We constructed the complete population using inverse probability of participation weights. Results Of 2328 survivors, 930 returned the initial questionnaire (40%); 671 returned the questionnaire after ≥1reminder (29%). Compared to early and late responders, we found that the 727 nonresponders (31%) were more likely male, aged

Objectives We evaluated whether interactive, electronic, dynamic, diagnose-specific checklists improve the quality of referral letters in gastroenterology and assessed the general practitioners’ (GPs’) acceptance of the checklists. Design Randomised cross-over vignette trial. Setting Primary care in Norway. Participants 25 GPs. Intervention The GPs participated in the trial and were asked to refer eight clinical vignettes in an internet-based electronic health record simulator. A referral support, consisting of dynamic diagnose-specific checklists, was created for the generation of referral letters to gastroenterologists. The GPs were randomised to refer the eight vignettes with or without the checklists. After a minimum of 3 months, they repeated the referral process with the alternative method. Main outcome measures Difference in quality of the referral letters between referrals with and without checklists, measured with an objective Thirty Point Score (TPS). Difference in variance in the quality of the referral letters and GPs’ acceptance of the electronic dynamic user interface. Results The mean TPS was 15.2 (95% CI 13.2 to 16.3) and 22.0 (95% CI 20.6 to 22.8) comparing referrals without and with checklist assistance (p

This is a pre-copyedited, author-produced version of an article accepted for publication in American Journal of Epidemiology following peer review. The version of record Ghiasvand, R., Rueegg, C.S., Weiderpass, E., Green, A.C., Lund, E. & Veierød, M.B. (2017). Ghiasvand et al. Respond to "Indoor Tanning-A Melanoma Accelerator?". American Journal of Epidemiology. 185(3), 160-161 is available online at: https://doi.org/10.1093/aje/kww150.

Background Beyond survival of nowadays >80%, modern childhood cancer treatment strives to preserve long-term health and quality of life. However, the majority of today’s survivors suffer from short- and long-term adverse effects such as cardiovascular and pulmonary diseases, obesity, osteoporosis, fatigue, depression, and reduced physical fitness and quality of life. Regular exercise can play a major role to mitigate or prevent such late-effects. Despite this, there are no data on the effects of regular exercise in childhood cancer survivors from randomized controlled trials (RCTs). Primary outcome of the current RCT is therefore the effect of a 12-months exercise program on a composite cardiovascular disease risk score in childhood cancer survivors. Secondary outcomes are single cardiovascular disease risk factors, glycaemic control, bone health, body composition, physical fitness, physical activity, quality of life, mental health, fatigue and adverse events (safety). Methods A total of 150 childhood cancer survivors aged ≥16 years and diagnosed ≥5 years prior to the study are recruited from Swiss paediatric oncology clinics. Following the baseline assessments patients are randomized 1:1 into an intervention and control group. Thereafter, they are seen at month 3, 6 and 12 for follow-up assessments. The intervention group is asked to add ≥2.5 h of intense physical activity/week, including 30 min of strength building and 2 h of aerobic exercises. In addition, they are told to reduce screen time by 25%. Regular consulting by physiotherapists, individual web-based activity diaries, and pedometer devices are used as motivational tools for the intervention group. The control group is asked to keep their physical activity levels constant. Discussion The results of this study will show whether a partially supervised exercise intervention can improve cardiovascular disease risk factors, bone health, body composition, physical activity and fitness, fatigue, mental health and quality of life in childhood cancer survivors. If the program will be effective, all relevant information of the SURfit physical activity intervention will be made available to interested clinics that treat and follow-up childhood cancer patients to promote exercise in their patients. Trial registration Prospectively registered in clinicaltrials.gov [ NCT02730767 ], registration date: 10.12.2015.